A central research theme of the Khalid group research is multiple scale simulation of bacterial cell envelopes. We are interested in their fundamental biochemistry as well as mechanisms of antimicrobial resistance to antibiotics (AMR). We develop in silico models with in vivo relevance.
Questions we have addressed include:
What are the molecular determinants of solute passage through specific proteins?
What are the free energies of permeation of small organic molecules across the E. coli outer membrane?
Do outer membrane proteins have lipid fingerprints?
What is the mechanism of inhibition of lipoprotein carriers by small hydrophobic molecules?
What role do non-covalent protein-cell. wall interactions play in painting the integrity of the cell envelope?
More recently we have become interested in issues of crowding within the bacterial cell envelope and understanding the spatial arrangements of macromolecules within the three compartments of that constitute the cell envelope (outer membrane, periplasm and inner membrane).
Other ongoing work in the area of bacterial cell envelopes includes studying:
Individual proteins that are known conduits for antibiotics at the atomistic level and quantum mechanical levels
Species-dependent differences in membrane composition and their biomedical implications in the context of antibiotic design and targeting development of resistance to antibiotics.
Atomistic simulations of systems that more accurately represent cell envelope in terms of composition and crowding level
Developing truly multiscale models that will enable the study of more mesoscopic behaviour such as build-up of biofilms.
Developing AI approaches to integrate molecular simulations and novel high volume microscopy methodologies.
Our ultimate aim is to develop a multiscale model that extends from the atomistic regime to the whole cell level: A VIRTUAL CELL ENVELOPE.